1. Field of the Invention
The present invention relates to a method for drawing a biological sample by means of a suction-discharge device, such as a pipette, either manual or automatic, and built into an automated device or not. It also relates to a process used to detect the free surface of a biological sample or a solid by means of a manual or automatic suction-discharge device, built into an automated device or not. Lastly, it relates to a sample drawing device, such as a pipette, and a device for detecting the free surface of a biological sample or a solid. Regardless of the device in question, it may be either manual or automatic, or built into an automated device or not.
This is a new method for detecting the level of a biological liquid in a specimen holder or test tube, particularly necessary on an automatic analyzer.
2. Description of the Related Art
The prior art shows that numerous methods are often used on other automated devices.
These methods may be electric.
Firstly, a reusable metal needle may be used which acts as an electrode, the second electrode being the liquid in which the needle will enter. When the needle comes into contact with the biological sample, a variation in impedance, capacitance or resistance, after amplification, triggers the shut-down of the needle lowering motor.
Secondly, a cone or conductive tip may be used which can be clipped on and thus disposed of after each sampling by the pipette associated with the cone. The latter are made of a plastic material which is loaded with carbon particles. The electrical connection is ensured by the cone gripping device which must be metallic.
Thirdly, other systems operate by adding to the needle or sampling cone, two electrodes placed on each side of the needle or cone, and ensuring electrical current conduction when these electrodes come into contact with the biologic liquid. This latter variant exhibits the major defect of contaminating the electrodes each time they come into contact with a new biologic liquid, thereby requiring the addition of a decontaminating washing system.
These methods may be optical.
Firstly, a camera may be used which displays the liquid level and when the needle comes into contact with the liquid.
Secondly, an optoelectronic system may also be used, featuring a photodetector which detects the liquid level and the needle""s contact with the liquid or the sampling point in the liquid.
According to all embodiments of the sampling means, associated with electronic or optical means, during the sampling operation, the needle or sampling tip enters the biological sample to be drawn. If the needle or tip enters too deeply into the liquid of the sample, there is, on the one hand, a risk of contamination from the exterior of the needle and, on the other hand, an xe2x80x9coverdosingxe2x80x9d, that is to say that the quantity of biological liquid having wetted the external wall of the needle or tip will be fully or partially released after transfer into the specimen holder, thereby distorting the exactness of the distributed dose.
There are, however, techniques which allow the tip used not be contaminated by the sampled liquid.
These methods may be acoustic. The patent U.S. Pat. No. 4,846,003 describes a detection system which uses an acoustic characteristic emitted by a speaker and received by a microphone. The value measured is established by the acoustic impedance.
Other documents, such as EP-A-0.341.438, U.S. Pat. No. 5,723,795, and EP-A-0.571.100, recommend the usage of pressure sensors. This system consists in detecting a pressure fluctuation, as soon as the free end of the tip comes into contact with the surface of a liquid.
Nevertheless, the sensors of these devices are associated with constantly uniform and unidirectional air movements. They do not allow for the evaluation of the numerous characteristics according to the present invention. The purpose of the invention is not only to detect a liquid or solid surface, a tip defect, and/or a leakage problem. The purpose of the invention includes the following:
to detect and to distinguish between the presence of a bubble or foam at the surface of a liquid sample to detect or to draw,
to detect a bubble, a solid impurity or an impurity having a different density in said sample;
to distinguish between a bubble (when detected) from foam (or foam from a bubble) at the surface of a liquid sample to detect or to draw;
to distinguish a bubble (when detected) from a solid impurity or from an impurity having a different density in said sample.
Moreover, the present invention may as well be used as a viscometer, as there is a relationship between the duration of the sampling operation, the vacuum pressure created within the pipette and measured by a pressure sensor, and the viscosity of the liquid sampled. The applicant has also filed a patent application, under number FR98/01376 dated Feb. 2, 1998, relating to: xe2x80x9cProcxc3xa9dxc3xa9 et dispositif de mesure de la viscositxc3xa9 d""un liquide et utilisation d""une pipette comme viscosimxc3xa8trexe2x80x9d (A process and device for measuring the viscosity of a liquid and the usage of a pipette as a viscometer). The contents of this patent application are incorporated in this invention.
Furthermore, current techniques, which prevent the needle or sampling tip from entering too deeply into the biological sample to be drawn, require the use of complex means (camera, carbon tips, etc.) for detecting the free surface of the sample; means which are thus expensive and make their distribution on the market limited.
The invention thus aims at solving all of these problems by offering devices which are easy to use. Such devices assist in doing away to a significant degree with problematic electrical contacts with the use of non-conductive disposable tips which are much less costly and less critical to manufacture, and with the reuse of a sensor already available for detecting needle clogging.
To this end, the present invention concerns a method for drawing a biological sample by means of a suction-discharge device, such as a manual or automatic pipette, built into an automated device or not, characterized in that it includes:
actuating a means causing a pressure variation and/or a flow of air within the device,
positioning the lower free end of said suction-discharge device in such a way that it is flush with the free surface of the biological sample,
measuring overpressure, due to the flushness of the lower free end of said device with the free surface of the biological sample, and
drawing a quantity of said sample by suction using the device.
The present invention also concerns a method for detecting the free surface of a biological sample or of a solid by means of a manual or automatic suction-discharge device, built into an automated device or not, characterized in that it includes:
actuating a means causing, within the device, a pressure variation and/or air flow which corresponds to the idle state of said device, and
detecting a pressure, within the suction-discharge device, which is different from the pressure variation or air flow when idle, this pressure corresponding to the position in which the lower free end of said device is flush with the free surface of the sample or solid.
In all cases, the suction-discharge volume variation ranges from a few nanoliters (nl) to a few microliters (xcexcl), and/or the constant pressure variation, otherwise referred to as frequency, ranges from a few Hertz to a few hundred Hertz (Hz).
In all cases, the air flow ranges from 10 to 50 xcexcl per second, and preferably from 20 to 30 xcexcl per second.
Furthermore, a pressure variation different from the pressure variation normally created by the means that generates this variation, before coming into flush contact, allows the following to be detected:
a sampling tip anomaly,
the presence of said tip on the pipette, and/or
the presence of at least one air bubble in the sample, or on the surface of the sample.
Likewise, a pressure variation in relation to the measured pressure, when the air flow is created, allows the following to be detected:
at least one air bubble, in the case where a pressure plateau is detected following an initial pressure variation, or
a free surface of a liquid, in the case where a second pressure variation follows the first pressure variation, or
a surface of a solid in the case where there is only a pressure increase.
A pressure variation must be interpreted as consisting of a pressure increase followed by a pressure decrease or by a pressure decrease followed by a pressure increase, which generates a peak.
The invention also concerns a device for drawing a biological sample, such as a manual or automatic pipette, built into an automated device or not, characterized by the fact that it features:
at least a means for creating a pressure variation or an air flow within the device at rest,
at least a pressure sensor for measuring, on the one hand, the pressure variation at rest or a pressure different from this pressure variation or, a pressure different from the pressure created by the air flow within the device, on the other hand, and
means for analyzing measurement parameters from the sensor(s) to enable the sampling operation to take place, when the lower free end of said suction-discharge device is flush with the free surface of the biological sample.
According to a special embodiment, the device used to detect the free surface of a biological sample or a solid is manual or automatic, and is built into an automated device or not; it features:
at least a means for generating a pressure variation or an air flow within the device at rest,
at least a pressure sensor for measuring, on the one hand, the pressure variation at rest or a pressure different from this pressure variation, or a pressure different from the pressure created by the air flow within the device on the other hand, and
means for analyzing measurements from the sensor(s) used to detect when the lower free end of the suction-discharge device becomes flush with the free surface of the biological sample or a solid.
The means for creating a pressure variation consists of a flexible tube which can be compressed and decompressed regularly by any reciprocating movement type mechanism, such as a cam or crank associated with a motor.
The means creating the air flow consists of the pipette piston, when it ejects the air outside said pipette.
The lower free end of the device is made up of a disposable tip.